Over the past twenty years, nuclear magnetic resonance imaging (MRI) has developed into an important modality for both clinical and basic-science imaging applications. Nonetheless, advancements continue at a rapid pace. A recent notable advance was the introduction of “hyperpolarized” noble gases as new contrast agents [1]. Under typical experimental conditions, the nuclear polarization for MRI (to which the signal level, or in more general terms, the image quality, is proportional) is at most on the order of 10−4, whereas polarizations approaching 100% are possible with hyperpolarized gases. Therefore, considering that in general nuclear magnetic resonance (NMR) is inherently limited by the available signal-to-noise ratio, hyperpolarized gases present the possibility for applications that were heretofore not feasible.
Of particular interest for hyperpolarized-gas NMR studies are the two non-radioactive noble-gas isotopes with a nuclear spin of 1/2, helium-3 and xenon-129. Both nuclei are useful for imaging of gas-filled spaces, such as cracks and voids in materials [2], or the lungs and sinuses in humans and animals [1]. Xenon-129 is soluble in a variety of substances, while helium-3 in general has a very low solubility [3]. In particular, xenon is lipophilic, having a high solubility in oils and lipid-containing tissues. Another important characteristic of xenon-129 is an exquisite sensitivity to its environment that results in an enormous range of chemical shifts upon solution (e.g., a range of approximately 200 ppm in common solvents) or adsorption [4]. These solubility and chemical shift characteristics make xenon-129 a valuable probe for a variety of material science and biological applications.
The behavior of xenon when inhaled by a human or an animal is a particularly interesting and important example to consider. Inhaled xenon dissolves rapidly into the bloodstream and is transported throughout the body, with preferential distribution to lipid-rich regions. Thus, dissolved-phase MRI of hyperpolarized xenon-129 may allow perfusion imaging of the brain, lung, and other organs, and offers the potential for the non-invasive characterization of other important physiological parameters. Although direct, high-resolution, dissolved-phase in-vivo MR imaging of xenon-129, particularly in humans, has remained elusive, the xenon polarization transfer contrast (XTC) MRI technique [5] has provided the means to generate high-resolution MR images of gaseous xenon-129 whose contrast reflects the characteristics of xenon gas-exchange between gas and dissolved-phase compartments. For example, in the lung, XTC MRI takes advantage of the rapid gas exchange between the lung parenchyma and the alveolar airspaces, and the large chemical-shift difference between dissolved and gaseous xenon, to manipulate the dissolved-phase magnetization by using radio-frequency pulses and subsequently observe the changes in the gas-phase magnetization. Depending on the pulse-sequence parameters that are chosen, the resulting gas-depolarization maps can be made to reflect various lung physiological parameters such as the lung tissue volume, the alveolar surface-to-volume ratio or the blood volume in the alveolar capillary beds [6].
Despite the inherent flexibility of XTC MRI and its potential for yielding, for example in the lung, information of physiological and medical relevance, the technique provides suboptimal sensitivity due to the relatively low signal-to-noise ratio and the low temporal resolution (several seconds) for the implementations that have been developed to date. Thus, it would be highly desirable to develop an MR technique that generates high-resolution images, whose contrast reflects gas-exchange properties as is possible with XTC MRI, but that also yields a much higher signal-to-noise ratio and sub-second temporal resolution.